Functional analysis of Ectodysplasin-A mutations causing selective tooth agenesis
| Autor: | Laure Willen, Sylvia A. Frazier-Bowers, Gabriele Mues, Hitesh Kapadia, Rena N. D'Souza, Pascal Schneider, Aubry Tardivel, Robyn Seaman |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Models Molecular Selective tooth agenesis Mutant DNA Mutational Analysis Molecular Sequence Data Biology Homology (biology) Article Cell Line 03 medical and health sciences 0302 clinical medicine Genetics medicine Humans Hypohidrotic ectodermal dysplasia Amino Acid Sequence Child Gene Genetics (clinical) 030304 developmental biology 0303 health sciences Dentition Sequence Homology Amino Acid Edar Receptor Tooth Abnormalities 030206 dentistry Ectodysplasins medicine.disease Cell biology Pedigree Phenotype Agenesis Mutation Ectodysplasin A Female Mutant Proteins Ectodysplasins/chemistry Ectodysplasins/genetics Edar Receptor/metabolism Mutant Proteins/metabolism Mutation/genetics Tooth Abnormalities/genetics |
| Zdroj: | Eur J Hum Genetics European Journal of Human Genetics, vol. 18, no. 1, pp. 19-25 |
| DOI: | 10.17615/78w5-kv54 |
| Popis: | Mutations of the Ectodysplasin-A (EDA) gene are generally associated with the syndrome hypohidrotic ectodermal dysplasia (MIM 305100), but they can also manifest as selective, non-syndromic tooth agenesis (MIM300606). We have performed an in vitro functional analysis of six selective tooth agenesis-causing EDA mutations (one novel and five known) that are located in the C-terminal tumor necrosis factor homology domain of the protein. Our study reveals that expression, receptor binding or signaling capability of the mutant EDA1 proteins is only impaired in contrast to syndrome-causing mutations, which we have previously shown to abolish EDA1 expression, receptor binding or signaling. Our results support a model in which the development of the human dentition, especially of anterior teeth, requires the highest level of EDA-receptor signaling, whereas other ectodermal appendages, including posterior teeth, have less stringent requirements and form normally in response to EDA mutations with reduced activity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|